This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. The purpose of this proposal is to clarify the clinical impact of a decline of kidney function on the risk of cardiovascular (CV) events in patients overweight or obese. Recent reports have demonstrated that in the general population, being overweight or obese is a known risk factor for CV events and death. Paradoxically, a large body of evidence has shown that in the population of end-stage renal disease (ESRD) patients, a high body mass index (BMI) seems to provide a longer survival, compared to a BMI25. However, in the general population studies, individuals are followed up for 15 to 30 years whereas ESRD patients have a much shorter life expectancy. Moreover, all the studies conducted in the ESRD population have been based on BMI reported at initiation of hemodialysis. It is well known that prior to hemodialysis, patients with low kidney function often experience weight loss because of uremia-induced anorexia or severe exacerbation of comorbidities. Patients with normal or low BMI at dialysis'initiation may be in fact patients who are in the process of losing weight because of poor health. Whether obesity is also more likely to be associated with longer survival in patients with a decrease in kidney function prior to the stage of ESRD is unclear. We propose to examine the association between BMI and kidney function on the risk of CV events in a population of patients followed for their clinical care in several out-patient clinics in Delaware, all using electronic medical records. This study will be a retrospective longitudinal analysis of patients. We will first determine whether a longitudinal decline in kidney function modifies the association between obesity and CV events (aim 1). To do so, we will develop longitudinal models of BMI and BMI + kidney function, and cross-correlate each of these with CV cumulative event rates. Similar cross-correlation patterns would indicate that kidney function does not modify the association between obesity and CV events. Then, we will determine the effects of weight changes prior to the initiation of hemodialysis on CV events rates in patients in hemodialysis (aim 2). To do so, we will use a Cox proportional hazard regression model to estimate hazard ratios for weight change and other covariates potentially influencing cardiovascular event rates potentially influencing cardiovascular event rates.